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Ketotifen

Updated · 20 sources

Ketotifen is an antihistamine and mast-cell stabilizer studied since the early 1980s to prevent asthma and treat allergic conditions. In the US it is approved only as over-the-counter eye drops for itchy eyes; oral tablets and syrup (Zaditen) are prescription drugs in other countries. In bodybuilding circles it is taken with clenbuterol on the idea that it stops beta-2 receptors from “downregulating,” so that clenbuterol keeps working without breaks.

That idea comes from 1980s and 1990s studies in rats, guinea pigs and healthy volunteers taking asthma drugs such as terbutaline, where ketotifen prevented or reversed beta-2 receptor desensitization in blood cells, airways and the heart. No study has tested whether ketotifen preserves clenbuterol’s effects on fat loss or muscle, and the heart data suggest it may also preserve clenbuterol’s cardiac stimulation. Oral ketotifen commonly causes sedation and weight gain.

This page summarizes what the labels, trials and receptor studies report. It is for education only and is not medical advice.

Property Detail
Drug class H1-antihistamine with mast-cell-stabilizing (“anti-anaphylactic”) activity
Brands Zaditen (oral tablets and solution, outside the US); Zaditor and Alaway (eye drops, US)
US status Eye drops 0.025% (ketotifen fumarate 0.035%) sold over the counter; no FDA-approved oral product
First FDA approval Zaditor eye drops, NDA 021066, July 2, 1999
Oral dose (Zaditen leaflet) Adults 1 mg twice daily with food, up to 2 mg twice daily; easily sedated patients start with 0.5–1 mg at night
Half-life Mean about 12 h (range 7–27 h) after a 2 mg oral dose
Main oral side effects Drowsiness, weight gain, dry mouth, dizziness; agitation and insomnia in children
Key cautions Avoid with oral antidiabetic drugs of the biguanide class (thrombocytopenia); lowers seizure threshold; adds to sedatives and alcohol
Clenbuterol use Based on receptor studies with other beta-2 agonists; untested for fat loss or muscle outcomes
WADA status Not prohibited; clenbuterol is prohibited at all times (S1.2)

What it is

Ketotifen has been studied for asthma prevention since at least the early 1980s. A 1990 review described it as an orally active preventive agent with “pronounced antihistaminic and antianaphylactic properties.” After 6 to 12 weeks, it reduced respiratory symptoms in about 70% and the need for other asthma drugs in about 50% of patients with mild to moderate asthma, though improvement in lung function was “generally slight” (Grant et al., Drugs 1990).

It has two main actions:

  • H1 receptor blockade. It blocks histamine at H1 receptors, the receptors behind itching, sneezing and swelling in allergic reactions. Drowsiness is a common side effect of oral use.
  • Mast-cell stabilization. Mast cells are immune cells that release histamine and other mediators during allergic reactions. Ketotifen is described as a mast-cell stabilizer, though in an irritable bowel syndrome trial it did not change histamine or tryptase release from gut biopsies, and the authors could not say whether its benefit came from mast-cell stabilization or H1 blockade (Klooker et al., Gut 2010).

Pharmacokinetics

In two crossover studies in 40 healthy men given 2 mg as capsules or syrup, ketotifen was absorbed quickly, reaching peak levels of about 300–400 pg/mL within 2 to 4 hours. The terminal half-life varied between people from 7 to 27 hours, with a mean of about 12 hours (Grahnén et al., Biopharm Drug Dispos 1992). Asthma benefits take weeks to appear, and the 1990 review noted that a “lengthy run-in period” is needed (Grant et al., 1990).

Approved medical use

United States: eye drops only

The FDA first approved ketotifen as Zaditor eye drops in 1999 (openFDA, NDA 021066). Ketotifen eye drops are now sold over the counter under several brands, including Zaditor and Alaway. The OTC label lists one use: temporary relief of itchy eyes due to pollen, ragweed, grass, animal hair and dander, at 1 drop in the affected eye twice daily for adults and children 3 years and older (Zaditor label). Drugs@FDA lists only ophthalmic ketotifen products; no oral form is FDA-approved.

Other countries: oral tablets and solution

Oral ketotifen is sold as Zaditen in several countries. In Ireland, the patient leaflet describes it as an anti-allergic medicine used for conditions such as rhinitis, with an adult dose of 1 mg twice daily with food, increasable to 2 mg twice daily. Children over 3 take 1 mg twice daily (Zaditen leaflet, HPRA).

What the research shows

Asthma in children

A Cochrane review of 26 randomized trials (1,826 children, 4 months to 18 years) found more children on ketotifen could reduce or stop bronchodilator use after 12–16 weeks (relative risk 2.39, 95% CI 1.64–3.48). Several secondary benefits did not hold up in the best-blinded trials. Sedation (21% vs 12%) and weight gain (27% vs 17%) were more common than with placebo (Schwarzer et al., Cochrane 2004).

Irritable bowel syndrome

In a randomized trial of 60 patients with irritable bowel syndrome, 8 weeks of ketotifen raised the threshold for rectal discomfort in patients with visceral hypersensitivity (an exaggerated gut pain response), reduced abdominal pain and other symptoms, and improved quality of life compared with placebo (Klooker et al., Gut 2010).

Weight

Weight gain is a recognized effect, and it has been tested as a goal. In an open-label study of 6 HIV-infected patients, 4 mg/day for 84 days lowered TNF-alpha release from blood cells in the lab, and patients gained 2.7 kg, then lost 1.6 kg after stopping (Ockenga et al., Eur J Clin Pharmacol 1996). The study had no control group.

Beta-2 receptor desensitization: the basis for use with clenbuterol

Beta-2 agonists such as clenbuterol, albuterol and terbutaline act on beta-2 adrenergic receptors. With continuous use, cells reduce their response, a process called desensitization or tachyphylaxis, partly by removing receptors from the cell surface (downregulation). Several studies tested whether ketotifen can block this:

Study Model Beta agonist Finding with ketotifen
Bretz et al., Eur J Pharmacol 1983 Rats with continuous infusion pumps Isoprenaline One dose reversed tachyphylaxis; continuous ketotifen prevented it. In isolated guinea pig trachea the effect looked like direct potentiation rather than reversal
Brodde et al., J Clin Invest 1985 36 healthy volunteers; white blood cells (lymphocytes) Oral terbutaline 5 mg three times daily Terbutaline cut lymphocyte beta-2 receptor density by 40–50%. Ketotifen (2 mg, then 1 mg twice daily) restored density within 24 h of stopping terbutaline and, given together, completely prevented the loss
Koshino et al., Biochem Biophys Res Commun 1988 Guinea pig lung Terbutaline Prevented receptor loss in a dose-dependent way; ketotifen alone also increased receptor density
Brodde et al., Eur J Clin Pharmacol 1988 13 asthmatic patients on beta-2 bronchodilators Their usual inhalers 1 mg twice daily for 6 days restored lymphocyte receptor density and response to normal; peak flow improved
Pauwels and Van der Straeten, J Allergy Clin Immunol 1988 10 healthy volunteers, double-blind crossover Inhaled salbutamol (albuterol) Prevented further bronchial tachyphylaxis; could not show it restored sensitivity already lost
Huszar et al., Z Erkr Atmungsorgane 1990 Asthmatic patients after 3 months of clenbuterol Clenbuterol (Spiropent) Clenbuterol alone did not reduce lymphocyte receptor function; adding ketotifen for 1 week increased it above healthy controls
Brodde et al., J Cardiovasc Pharmacol 1992 10 healthy volunteers, double-blind, placebo-controlled Oral terbutaline 14 days Markedly blunted loss of beta-2 effects (blood pressure and noradrenaline responses); beta-1 effects were not desensitized
Poller et al., Cardiovasc Res 1998 10 healthy men, single-blind crossover Oral terbutaline 2 weeks Reduced the loss of beta-2-mediated heart rate and contractility responses
Schäfers et al., Br J Clin Pharmacol 1999 10 healthy men, double-blind Xamoterol (beta-1 partial agonist) No effect on beta-1 responses

What these studies support. Ketotifen at 1–2 mg/day, the usual antiallergy dose, can prevent or partly reverse desensitization of beta-2 receptors in lymphocytes, airways and the heart during treatment with terbutaline or salbutamol. The authors framed this as a way to prevent tolerance to asthma inhalers.

What they do not show:

  • No study measured skeletal muscle or fat. Clenbuterol’s sought-after effects in sport come from beta-2 receptors in muscle and fat, and receptor regulation differs between tissues. In rats, clenbuterol reduced beta-2 receptors in skeletal muscle by 35%, and dexamethasone, which increased receptors in the lung, did not prevent the loss in muscle (Huang et al., J Anim Sci 2000). Results in lung or blood cells may not carry over to muscle.
  • No study measured fat loss, energy expenditure, lean mass or performance with clenbuterol plus ketotifen.
  • The one clenbuterol study was small and did not show downregulation to begin with. In asthmatics on long-term clenbuterol, lymphocyte receptor function was no lower than in healthy people (Huszar et al., 1990).

Muscle tolerance to clenbuterol is real in people. In a 2025 randomized crossover trial, 11 healthy men took clenbuterol 80 µg/day or placebo for 2 weeks. Clenbuterol added 0.91 kg of lean mass but did not change fat mass, cut maximal oxygen uptake by 7%, and its activation of beta-2 signaling in muscle declined over the 2 weeks, which the authors described as tolerance (Hostrup et al., J Physiol 2025). Whether ketotifen would change any of this has not been tested.

A safety concern: the heart

Desensitization also blunts beta-2 effects in the heart. In the Poller study, ketotifen reduced the loss of terbutaline’s effects on heart rate and contractility (Poller et al., 1998), and in the Brodde 1992 study it blunted the loss of terbutaline’s effect on diastolic blood pressure and noradrenaline release (Brodde et al., 1992). If ketotifen has the same effect with clenbuterol, it could keep clenbuterol’s fast heart rate and other cardiovascular effects from fading. That combination has not been studied, and clenbuterol’s cardiac risks are covered on the clenbuterol page.

Side effects and risks

Oral ketotifen

Effect Evidence
Sedation, drowsiness 21% vs 12% placebo in children with asthma (Schwarzer et al., 2004); “can be troublesome in older children and adults for the initial 2 weeks” (Grant et al., 1990)
Weight gain 27% vs 17% placebo in children (Schwarzer et al., 2004); listed as “rare” in the Zaditen leaflet
Agitation, irritability, insomnia, nervousness Common (1–10 in 100), particularly in children
Dizziness, dry mouth, cystitis Uncommon (under 1 in 100)
Headache, nausea, vomiting, diarrhea, rash, hives Reported, frequency not known
Convulsions Reported very rarely; ketotifen may lower the seizure threshold

Source unless noted: Zaditen leaflet, HPRA. The leaflet says sleepiness, dry mouth and dizziness usually pass after a few days, and advises not to drive until the effect on reactions is known.

The sedation and weight gain are directly at odds with the goals of a clenbuterol “cutting” cycle.

Interactions and who should not take it

From the Zaditen leaflet (HPRA):

  • Oral diabetes drugs: the leaflet says not to take Zaditen with oral diabetes medicines, and that thrombocytopenia (low platelets) may occur with biguanides, the class that includes metformin.
  • Epilepsy: contraindicated.
  • Breastfeeding: contraindicated; ketotifen passes into breast milk.
  • Sedatives, other antihistamines, antidepressants, anxiety medicines and alcohol: effects may be increased.
  • Anticoagulants: the leaflet lists them among medicines whose effects may be increased.
  • Asthma medicines: do not stop them when starting ketotifen.

Eye drops

The OTC eye drops are for use in the eye only. The label advises removing contact lenses before use and stopping if eye pain, vision changes, redness or worsening itch occur (Zaditor label). Eye drops are not a substitute for oral dosing in any of the receptor studies.

In the US, ketotifen is available only as OTC eye drops; oral ketotifen is not an FDA-approved product. In several other countries, oral Zaditen is a prescription medicine.

Ketotifen is not on the WADA 2026 Prohibited List. Clenbuterol is named under S1.2 (other anabolic agents) and is prohibited at all times, in and out of competition. Taking ketotifen does not change that.

Key takeaways

  • An antihistamine and mast-cell stabilizer. Ketotifen is used for asthma prevention and allergies abroad; in the US it is approved only as OTC eye drops.
  • The clenbuterol rationale has a real basis, but in other tissues. Studies from 1983 to 1998 showed ketotifen prevents beta-2 receptor desensitization in lymphocytes, airways and the heart during terbutaline or salbutamol use.
  • Nothing shows it preserves clenbuterol’s fat-loss or muscle effects. No study measured beta-2 receptors in muscle or fat, or body composition, with the combination.
  • It may keep cardiac effects from fading. In volunteers, ketotifen reduced the loss of terbutaline’s heart rate and contractility effects.
  • Sedation and weight gain are common. In pediatric trials, 21% had sedation and 27% gained weight, vs 12% and 17% on placebo.
  • Watch interactions. Avoid with biguanides such as metformin (low platelets), epilepsy and alcohol or sedatives; clenbuterol stays prohibited in sport regardless.

Sources

  1. Grant SM, Goa KL, Fitton A, et al. Ketotifen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma and allergic disorders. Drugs. 1990;40(3):412–448. PubMed.
  2. Grahnén A, Lönnebo A, Beck O, et al. Pharmacokinetics of ketotifen after oral administration to healthy male subjects. Biopharm Drug Dispos. 1992;13(4):255–262. PubMed.
  3. US Food and Drug Administration. Drugs@FDA data for Zaditor (ketotifen fumarate ophthalmic solution), NDA 021066, and other ketotifen applications. Accessed November 2026. openFDA.
  4. Alcon Laboratories. Zaditor (ketotifen fumarate ophthalmic solution) OTC drug facts label. DailyMed.
  5. Health Products Regulatory Authority (Ireland). Zaditen 1 mg tablets: package leaflet. 2025. HPRA.
  6. Schwarzer G, Bassler D, Mitra A, et al. Ketotifen alone or as additional medication for long-term control of asthma and wheeze in children. Cochrane Database Syst Rev. 2004;(1):CD001384. PubMed.
  7. Klooker TK, Braak B, Koopman KE, et al. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut. 2010;59(9):1213–1221. PubMed.
  8. Ockenga J, Rohde F, Süttmann U, et al. Ketotifen in HIV-infected patients: effects on body weight and release of TNF-alpha. Eur J Clin Pharmacol. 1996;50(3):167–170. PubMed.
  9. Bretz U, Martin U, Mazzoni L, et al. beta-Adrenergic tachyphylaxis in the rat and its reversal and prevention by ketotifen. Eur J Pharmacol. 1983;86(3-4):321–328. PubMed.
  10. Brodde OE, Brinkmann M, Schemuth R, et al. Terbutaline-induced desensitization of human lymphocyte beta 2-adrenoceptors. Accelerated restoration of beta-adrenoceptor responsiveness by prednisone and ketotifen. J Clin Invest. 1985;76(3):1096–1101. PubMed.
  11. Koshino T, Agrawal DK, Townley TA, et al. Ketotifen prevents terbutaline-induced down-regulation of beta-adrenoceptors in guinea pig lung. Biochem Biophys Res Commun. 1988;152(3):1221–1227. PubMed.
  12. Brodde OE, Howe U, Egerszegi S, et al. Effect of prednisolone and ketotifen on beta 2-adrenoceptors in asthmatic patients receiving beta 2-bronchodilators. Eur J Clin Pharmacol. 1988;34(2):145–150. PubMed.
  13. Pauwels R, Van der Straeten M. The effect of ketotifen on bronchial beta-adrenergic tachyphylaxis in normal human volunteers. J Allergy Clin Immunol. 1988;81(4):674–680. PubMed.
  14. Huszar E, Herjavecz I, Böszörmenyi-Nagy G, et al. Effects of ketotifen and clenbuterol on beta-adrenergic receptor functions of lymphocytes and on plasma TXB-2 levels of asthmatic patients. Z Erkr Atmungsorgane. 1990;175(3):141–146. PubMed.
  15. Brodde OE, Petrasch S, Bauch HJ, et al. Terbutaline-induced desensitization of beta 2-adrenoceptor in vivo function in humans: attenuation by ketotifen. J Cardiovasc Pharmacol. 1992;20(3):434–439. PubMed.
  16. Poller U, Fuchs B, Gorf A, et al. Terbutaline-induced desensitization of human cardiac beta 2-adrenoceptor-mediated positive inotropic effects: attenuation by ketotifen. Cardiovasc Res. 1998;40(1):211–222. PubMed.
  17. Schäfers RF, Karl I, Mennicke K, et al. Ketotifen and cardiovascular effects of xamoterol following single and chronic dosing in healthy volunteers. Br J Clin Pharmacol. 1999;47(1):59–66. PubMed.
  18. Huang H, Gazzola C, Pegg GG, et al. Differential effects of dexamethasone and clenbuterol on rat growth and on beta2-adrenoceptors in lung and skeletal muscle. J Anim Sci. 2000;78(3):604–608. PubMed.
  19. Hostrup M, Moesgaard L, Fischer M, et al. Clenbuterol induces lean mass and muscle protein accretion, but attenuates cardiorespiratory fitness and desensitizes muscle β2-adrenergic signalling. J Physiol. 2025;603(19):5529–5545. PubMed.
  20. World Anti-Doping Agency. The 2026 Prohibited List (in effect January 1, 2026). 2025. WADA.